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FIBROVEIN 1% SOLUTION FOR INJECTION

Active substance(s): SODIUM TETRADECYL SULPHATE / SODIUM TETRADECYL SULPHATE / SODIUM TETRADECYL SULPHATE

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SUMMARY OF PRODUCT CHARACTERISTICS
1

NAME OF THE MEDICINAL PRODUCT
Fibrovein 1% Solution for Injection

2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each ml solution for injection contains 10mg Sodium Tetradecyl Sulfate.
Each 2ml ampoule contains 20mg Sodium Tetradecyl Sulfate.
Contains benzyl alcohol 20mg/ml. For a full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Solution for injection.
Clear, colourless, sterile solution.
pH 7.5 – 7.9.
Osmolarity 247 – 273 mOsm/kg.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
For the treatment of uncomplicated primary varicose veins, recurrent or residual
varicose veins following surgery, reticular veins, venules and spider veins of the
lower extremities that show simple dilation.
Fibrovein is indicated in adults.

4.2

Posology and method of administration
Method of administration
Fibrovein is for intravenous use only. The strength of solution required depends on
the size and degree of varicosity. Spider veins should only be treated with the 0.2%,
reticular veins with 0.5%, the 1% solution will be found most useful for small to
medium varicosities and the 3% solution for larger varicosities. The size of nonvisible varicose veins should be measured under ultrasound.

The sclerosant should be administered intravenously in small aliquots at multiple sites
along the vein to be treated either as a liquid or as a sclerosant/air mixture (foam), for
the treatment of larger veins with the 1% and 3% solutions. The objective is to
achieve optimal destruction of the vessel wall with the minimum concentration of
sclerosant necessary for a clinical result. If the concentration is too high necrosis or
other adverse sequelae may occur.
Refer to the end of 4.2 and section to 6.6 for foam preparation.
The Tessari method of preparation of the foam is described. Other techniques may be
used e.g. DSS, Easyfoam and Sterivein most of which consist of mixing sclerosant
and sterile air by repeated passes through 2 connected syringes. Specific instructions
for handling are detailed in section 6.6.
Strict aseptic technique must be maintained while handling Fibrovein.
Fibrovein is a single-use parenteral product. Once the container is opened, use
immediately and discard any unused portion.
Visually inspect for particulate matter before use. Solutions that contain particulate
matter should not be used.
Recommended doses and dosage schedules
Adults/Elderly

Concentration

Fibrovein 1%

Normal volume injected
intravenously at suitable
sites per session
Liquid
Foam*

Liquid

Foam*

0.1 to 1.0 ml

10 ml

16ml

0.5 to 2.0ml

Maximum total volume to
be injected per session

* volume is the sum of the liquid and air components
Where special caution is indicated it is recommended that a test dose of 0.25 to 0.5ml
Fibrovein should be given followed by observation of the patient for several hours
before administration of a second or larger dose.
As the volume to be injected is limited per session, repeated sessions are usually
needed (2 to 4 on average). To prevent a possible allergic reaction, it is recommended
that a small test dose of Fibrovein should be given at the beginning of each session.
When the sclerosant is administered as a foam.
Fibrovein 1% and 3%, may be converted to a foam to be used for the treatment of
larger veins. The foam must be prepared just before use and administered by a

physician appropriately trained in the correct generation and administration of foam.
It should ideally be administered under ultra sound guidance.
Paediatric Population
Fibrovein is not indicated in children.

4.3 Contra-indications
Hypersensitivity to sodium tetradecyl sulfate or to any component of the preparation
and allergic conditions.
Patients unable to walk due to any cause, bedridden patients
Patients with a high risk of thrombosis e.g. patients with a congenital predisposition to
blood clots or with multiple risk factors such as hormonal contraception or hormone
replacement therapy, significant obesity, smoking or extended periods of immobility
Recent acute superficial thrombophlebitis, deep vein thrombosis or pulmonary
embolism
Recent surgery
Varicosities caused by pelvic or abdominal tumours unless the tumour has been
removed
Uncontrolled systemic disease such as diabetes mellitus, toxic hyperthyroidism,
tuberculosis, asthma, neoplasm, sepsis, blood dyscrasias and acute respiratory or
skin diseases
Evolutive cancer
Significant valvular incompetence of the deep veins
Occlusive arterial disease
Huge superficial veins with wide open communications to deeper veins
Phlebitis migrans
Acute cellulitis
Acute infections
In addition when the sclerosant has been converted to foam:
Known symptomatic patent foramen ovale (PFO).
4.4 Special warnings and special precautions for use
Fibrovein should only be administered by a healthcare professional experienced in
venous anatomy and the diagnosis and treatment of conditions affecting the venous
system and familiar with proper injection technique.
Before treatment, healthcare professional should investigate patient’s risk factors and
inform them about the risks of the technique.
As a reminder, sclerotherapy is contra-indicated in patients with high risk of
thromboembolic events, but should also be avoided in most situations at lower risk.
Sclerotherapy is notably not recommended in patients with a history of
thromboembolic events
Nevertheless, if sclerotherapy is judged necessary, preventive anticoagulation can be
initiated.

Due to the risk of circulation of product, bubbles or particulates in the right heart, the
presence of a PFO may enhance the occurrence of serious arterial adverse events. In
patients with history of migraine with aura, serious cerebrovascular events or
pulmonary hypertension, it is recommended to search for PFO before sclerotherapy.
In patients with asymptomatic but known PFO, it is recommended to use smaller
volumes and avoid Valsalva maneuver in the minutes after injection.
Use smaller volumes in patients with history of migraine.
Severe adverse local effects, including tissue necrosis, may occur following
extravasation; therefore, extreme care in intravenous needle placement and using the
minimal effective volume at each injection site are important.
Sclerosants must never be injected into an artery as this can cause extended tissue
necrosis and may result in loss of the extremity. Injection under duplex ultrasound is
recommended in order to avoid extravasations and arterial injection.
Healthcare professional should monitor the patient during and after the administration
of Fibrovein. Symptoms of hypersensitivity (redness, pruritis, cough) or neurological
symptoms (scotoma, amaurosis, migraine with aura, paresthesia, focal deficit) may
happen.
Special care should be taken in patients with laboured breathing (bronchial asthma) or
a strong predisposition to allergies (see section 4.2).
Emergency resuscitation equipment should be immediately available. Allergic
reactions, including anaphylaxis have been reported. The possibility of an
anaphylactic reaction should be kept in mind, and the physician should be prepared to
treat it appropriately.
Because of the danger of thrombosis extension into the deep venous system, thorough
preinjection evaluation for valvular competency should be carried out and slow
injections with a small amount (not over 2 mL) of the preparation should be injected
into the varicosity. Deep venous patency must be determined by noninvasive testing
such as duplex ultrasound. Venous sclerotherapy should not be undertaken if tests
such as Trendelenberg and Perthes, and angiography show significant valvular or
deep venous incompetence.
Healthcare professional should see the patient again after 1 month for a control of
treatment efficacy and safety, by clinical and ultrasound evaluation.
The development of deep vein thrombosis and pulmonary embolism have been
reported following sclerotherapy treatment of superficial varicosities. Patients should
have post-treatment follow-up of sufficient duration to assess for the development of
deep vein thrombosis. Embolism may occur as long as four weeks after injection of
sodium tetradecyl sulfate. Adequate post-treatment compression may decrease the
incidence of deep vein thrombosis.
Extreme caution in use is required in patients with underlying arterial disease such as
severe peripheral atherosclerosis or thromboangiitis obliterans (Buerger's disease).

Special care is required when injecting the foot and malleolar area where the risk of
inadvertent injection into an artery may be increased.
Pigmentation may be more likely to result if blood is extravasated at the injection site
(particularly when treating smaller surface veins) and compression is not used.
In addition when the sclerosant has been converted to foam:
Known asymptomatic patent foramen ovale (PFO). -Patients with a PFO have been
shown to be more likely to suffer from adverse events such as temporary neurological
events, visual disturbances and migraine.
Previous migraine sufferers should be treated with care. Patients with previous
migraine have been shown to be more likely to suffer from visual disturbances and
migraine, particularly following injections with foamed sclerosant.
For the treatment of truncular varicosities, there should be a minimal distance of 8 to
10 cm between the site of foam injection and the saphenofemoral junction.
If venous insufficiency is associated with lymphoedema, the sclerosant injection may
worsen local pain and inflammation for days or several weeks. Patients should be
informed of this expected phase, which does not compromise efficacy.

4.5

Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed.

4.6 Fertility, pregnancy and lactation
Pregnancy
Safety for use in pregnancy has not been established. There are no or limited amount
of data from the use of sodium tetradecyl sulfate in pregnant women. Animal studies
are insufficient with respect to reproductive toxicity. Treatment should be postponed
until after childbirth.

Fibrovein should be used only when clearly needed for symptomatic relief and when
the potential benefits outweigh the potential hazards to the fetus.
Lactation
It is not known whether sodium tetradecyl sulfate is excreted in human milk. Caution
should be exercised when used in nursing mothers.
Fertility
It is not known whether sodium tetradecyl sulfate affects fertility.

4.7

Effects on ability to drive and use machines
A bandage and/or compression stockings may be added after treatment. This could
affect the ability to drive.

4.8 Undesirable effects
The most commonly reported side effects are pain on injection urticaria, superficial
thrombophlebitis and temporary skin pigmentation after treatment. Very rarely a
permanent discoloration may remain along the path of the sclerosed vein segment.
Ulceration may occur following extravasation of the drug. It is important to use the
lowest strength that will sclerose the vein as many of the common side effects are
caused by using a concentration that is too high.
Intra-arterial injection although very rare has been reported resulting in significant
tissue necrosis including loss of the extremity.
The most serious side effects are anaphylactic shock and pulmonary embolism and
deaths have been reported in patients receiving sodium tetradecyl sulfate.
Adverse events are listed below by system organ class and estimated frequency from
published clinical data. Frequencies are defined using the following convention:
Very common  1/10
Common  1/100 to < 1/10
Uncommon  1/1000 to < 1/100
Rare  1/10,000 to < 1/1000
Very rare (includes isolated reports)  1/10,000
Immune disorders

Using liquid

Using foam

Systemic allergic reactions e.g. anaphylactic shock, asthma,
generalised hives.

Very Rare

Very Rare

Nervous system disorders
Headache, migraine, local sensitivity disturbances (parasthesias).
Vaso-vagal reactions e.g. fainting, confusion, dizziness, loss of
consciousness.
Nerve damage after extravasation of the drug
Weakness (hemiparesis, hemiplegia), transient ischaemic attack
(TIA), palpitations.
Stroke

Using liquid
Very Rare

Using foam
Rare

Very Rare
Very Rare

Very Rare
Very Rare

Very Rare

Very Rare

Eye disorders
Scotoma, scintillating scotoma.

Using liquid
Very rare

Using foam
Uncommon

Vascular disorders
Superficial thrombophlebitis, phlebitis.
Matting (growth of very fine spider veins in treated area).

Using liquid
Common
Uncommon

Using foam
Very Common
Common

Deep vein thrombosis (mostly muscular and distal).
Pulmonary embolism, vasculitis, circulatory collapse.
Distal tissue necrosis following intra-arterial injection, may lead
to gangrene. Most cases have involved the posterior tibial artery
above the medial malleolus. Arterial spasm can occur despite
intravenous injection.

Very rare
Very Rare
Very Rare

Uncommon
Very Rare
Very Rare

Respiratory disorders
Coughing, shortness of breath, sensation of pressure/tightness in
the chest.

Using liquid
Very rare

Using foam
Rare

Gastro-intestinal disorders
Nausea, vomiting, diarrhoea, feeling of swollen/thick tongue, dry
mouth.

Using liquid
Very rare

Using foam
Very rare

Skin and subcutaneous tissue disorders
Skin discolouration (hyperpigmentation, more rarely haematoma & ecchymosis).
Local allergic and non-allergic skin reactions e.g. erythema,
urticaria, dermatitis, swelling/induration.
Local sloughing and necrosis of skin & tissues.
General disorders
Pain or burning (short term at the injection site).
Fever, hot flushes.

4.9

Using liquid
Uncommon

Using foam
Common

Uncommon

Uncommon

Rare

Rare

Using liquid
Common
Very rare

Using foam
Uncommon
Very rare

Overdose
No case of systemic overdose has been reported. Using a higher concentration than
recommended in small veins may lead to pigmentation and/or local tissue necrosis.

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Sclerosing agents for local injections.
ATC code C05BB04
Sodium tetradecyl sulfate is a sclerosing agent. Intravenous injection causes intima
inflammation and thrombus formation. This usually occludes the injected vein.
Subsequent formation of fibrous tissue results in partial or complete vein obliteration
that may or may not be permanent.
5.2 Pharmacokinetic properties
Absorption
Fibrovein containing sodium tetradecyl sulfate is administered directly into the lumen
of the isolated segment of vein/venule.

Distribution
In humans, the majority (75%) of an injected dose of radiolabelled 3% sodium
tetradecyl sulfate rapidly disappeared from the empty varicose vein injection site into
communicating blood vessels with rapid passage into the deep calf veins.
In rats, at 72 hours after intravenous dosing of radiolabelled sodium tetradecyl sulfate,
tissue levels of radiolabel found in the sampled tissues (liver, kidney, lipid and
skeletal muscle) were extremely low. Although there was some evidence of radiolabel
associated with the injection site, the levels were very low.
Biotransformation
The metabolism of sodium tetradecyl sulfate has not been confirmed.
Elimination
Of an intravenously administered radiolabelled dose, 70% was recovered in the urine
of rats within the first 24 hours post-dosing. At the end of the 72 hour post-dose
period, 73.5% of the radiolabel had been recovered from the urine and 18.2%
recovered from the faeces.
Hepatic/Renal Impairment
No pharmacokinetics studies have been performed in patients with hepatic or renal
impairment.
5.3

Preclinical safety data
There are no additional data of relevance to the prescriber other than those already
mentioned in other sections of the SmPC.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Benzyl alcohol
Disodium phosphate dodecahydrate
Potassium dihydrogen phosphate
Sodium hydroxide (for pH adjustment)
Water for injections

6.2

Incompatibilities
This product is not compatible with heparin.

In the absence of compatibility studies, this medicinal product should not be mixed
with other medicinal products.

6.3

Shelf life
3 years.
After first opening, the product should be used immediately.

6.4

Special precautions for storage
This medicinal product does not require any special storage conditions.
Do not freeze. Keep the ampoule in the outer carton in order to protect from light.

6.5

Nature and contents of container
2ml ampoule (Type 1 glass). Pack size 5 ampoules.

6.6 Instructions for handling and disposal
The foam must be prepared just before use and administered by a physician
appropriately trained in the correct generation and administration of foam.
Strict aseptic technique must be maintained while manufacturing the foam.
Manufacture of foam using the Tessari technique
To create the foam 1ml of liquid sclerosant is drawn into a sterile syringe and 3ml or
4ml of sterile air is drawn into another sterile syringe. The air is drawn through a 0.2
μm filter to ensure it is sterile. The syringes are then connected using a sterile three
way tap/valve (Fig. 1).
The sclerosant/air mixture is then forced back and forth from one syringe to the other
through the 3-way valve approximately 20 times to produce a smooth, consistent foam
(Fig. 2&3).
The syringe containing the foam, is then removed and the vein is injected immediately
(Fig. 4).
The sclerosant foam must be used within sixty seconds of production. After sixty
seconds any remaining foam should be discarded. More foam should be prepared if
required.
The quality of the foam should be checked before administration. It should appear
homogeneous with no large bubbles visible to the naked eye.

Figure 1

Figure 2

Figure 3

Figure 4

The quality of foam depends on specific criteria:
1. The product concentration: Foam can only be prepared with concentrations of 1 to
3% sodium tetradecyl sulfate.
2. The proportion of liquid to air: Usually, this proportion is 1 volume of liquid for 3
volumes of air.
3. Number of backwards and forwards passes: The physician should follow precisely
the number of movements defined for each technique.
4. Macroscopic consistency of the foam: The quality of the foam should be checked
outside the syringe before administration. The foam should be homogenous, soft
and cohesive with no visible large bubbles. If large bubbles are visible, the foam
should be thrown away and new foam prepared.
5. The total time of preparation of the foam: The preparation should take around 10
seconds from the first to the last backwards and forwards movement.
6. The maximum time between preparation and injection: The sclerosant foam must
be used within sixty seconds of production. After sixty seconds, any remaining
foam should be discarded. More foam should be prepared if required.

Disposal
There are no special requirements for disposal

7

MARKETING AUTHORISATION HOLDER
STD Pharmaceutical Products Ltd
Plough Lane

Hereford
HR4 0EL
United Kingdom

8

MARKETING AUTHORISATION NUMBER(S)
PL 00398/0206

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
09/10/2012

10

DATE OF REVISION OF THE TEXT
18/05/2015

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Source: Medicines and Healthcare Products Regulatory Agency

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